Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair

Laura A. Murray-Nerger, Joshua L. Justice, Pranav Rekapalli, Josiah E. Hutton, Ileana M. Cristea

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.

Original languageEnglish (US)
Pages (from-to)2044-2064
Number of pages21
JournalNucleic acids research
Volume49
Issue number4
DOIs
StatePublished - Feb 26 2021

All Science Journal Classification (ASJC) codes

  • Genetics

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